PDF(Pubmed)
Abstract：
Variants in SCN8A are associated with several diseases, including developmental and epileptic encephalopathy, intermediate epilepsy or mild-to-moderate developmental and epileptic encephalopathy, self-limited familial infantile epilepsy, neurodevelopmental delays with generalized epilepsy, neurodevelopmental disorder without epilepsy, hypotonia, and movement disorders. Herein, we report an 8-year-old Moroccan boy with intermediate epilepsy of unknown origin, intellectual disability, autism spectrum disorder, and hyperactivity. The patient presented a normal 46, XY karyotype and a normal comparative genomic hybridization profile. Whole-exome sequencing was performed, and heterozygous variants were identified in KCNK4 and SCN8A. The SCN8A variant [c.4499C > T (p.Pro1500Leu)] was also detected in the healthy mother and was classified as a variant of uncertain clinical significance. This variant occurs in a highly conserved domain, which may affect the function of the encoded protein. More studies are needed to confirm the pathogenicity of this novel variant to establish the effective care, management, and genetic counselling of affected individuals.
摘要：
SCN8A的变体与几种疾病相关，包括发育性脑病和癫痫性脑病，中度癫痫或轻度至中度发育性和癫痫性脑病，自限性家族性婴儿癫痫，伴有全身性癫痫的神经发育迟缓，没有癫痫的神经发育障碍，低张力,和运动障碍。在这里，我们报道了一名8岁的摩洛哥男孩，患有不明原因的中度癫痫，智力残疾,自闭症谱系障碍，和多动症。患者表现出正常的46，XY核型和正常的比较基因组杂交谱。进行全外显子组测序，在KCNK4和SCN8A中鉴定出杂合变体。SCN8A变体[c.4499C>T（p。Pro1500Leu）]也在健康母亲中检测到，并被归类为具有不确定临床意义的变体。这种变异发生在一个高度保守的结构域，这可能会影响编码蛋白质的功能。需要更多的研究来证实这种新变体的致病性，以建立有效的护理，管理,和受影响个体的遗传咨询。
